Dibenzo[b,e][1,4]diazepine-11-ones are useful intermediates in pharmaceuticals. Particularly, dibenzo[b,e][1,4]diazepine-11-ones are active as an antidepressant, antitumor and anticonvulsant agents. Dibenzo[b,e][1,4]diazepin-11-ones also serve as intermediates for the preparation of dibenzo[1,4]diazepines.
The known processes for preparing dibenzo[b,e][1,4]diazepine-1′-ones are based on the condensation of amino and halo compounds followed by the cyclization using palladium salts, which involves a number of steps.
Reference may be made to PCT Published Patent Application No. WO 2006/097449 wherein the dibenzo[b,e][1,4]diazepine-11-one ring is prepared by the condensation of anthranilic acid and o-bromo nitrobenzene in the presence of copper powder at 140° C. to obtain an intermediate which upon reduction, followed by cyclization, gives diazepine-one. The main drawback of this process is the use of amino and halo compounds which are not commercially available and that it involves more number of steps. Moreover, the cyclization step requires expensive palladium catalyst.
Another reference may be made to E. M. Beccalli et al., Tetrahedron (2005), Vol. 61, pp. 61-68, wherein the condensation of o-nitrobenzoyl chloride with o-iodoaniline gives an intermediate which upon intramolecular amination with palladium acetate and BINAP gives dibenzo[1,4]dazepin-11-one. Particularly, this method has a disadvantage of using hazardous benzoyl chloride and rarely available iodoaniline. Another drawback is the use of expensive palladium salt and BINAP as a catalyst. Moreover, the use of anhydrous toluene and extended reaction time (24 hrs), make the procedure inconvenient.
Yet another reference may be made to A. R. Hanze et al., J. Med. Chem. (1963), pp. 767-771, wherein dibenzo[b,e][1,4]diazepine-11-ones are prepared starting from anthranilic acid and o-bromonitrobenzene at 200° C. using n-amyl alcohol as a medium. The intermediate was then cyclized by heating at 250° C. This process has the drawback of using expensive amyl alcohol and higher temperature, which is very difficult to maintain on a large scale.
All the earlier reported processes involve more number of steps and use hazardous starting materials, carcinogenic hydrocarbon as a solvent, which is difficult to handle on large scale and also generate waste effluent. Moreover, palladium catalyst and BINAP are reported for cyclizations which are very expensive and have negative influence on the economy. In addition to this, the reactions require higher temperature (200-250° C.) which is very inconvenient on a large scale production. Although practical in the laboratory, all these methods have following disadvantages on a commercial scale.
1. Numbers of steps involved are more.
2. Use of hazardous and corrosive starting halides or acid chlorides.
3. Expensive reagents are used for cyclization.
4. Use of hydrocarbon solvent as a medium.
5. Higher temperature required for reaction.
6. Generates metal containing waste.
There exists therefore a need to provide a one step process for the preparation of substituted dihydrodibenzo[b,e][1,4]diazepine-11-ones which does not have the above-described disadvantages.